Visualizing RNA activity within brain tissues for efficient discovery of drugs

A group led by Assistant Professor Dan Ohtan Wang from Kyoto University's Institute for Integrated Cell-Material Sciences (iCeMS) in Japan successfully visualized RNA behavior and its response to drugs within the living tissue brain of live mice by labeling specific RNA molecules with fluorescent probes. Their study, published in Nucleic Acids Research, can potentially lead to faster, and more accurate screening processes for the discovery and development of new drugs.

RNA is a molecule that plays a key role within a living organism, holding information as to when, where and how much protein must be allocated, which is also responsible for controlling the biological reactions within a living cell. RNAs behave uniquely and are distributed unequally in each cell, existing more in some areas of the cell than others depending on environmental factors and cell conditions. In some cases, these chemical changes can put the cell's health at risk due to RNA disruption. However, it is unclear as to how the distribution of RNA molecules is regulated in the cell, and what causes them to act abnormally.

By introducing a non-toxic, fluorescent probe within the brain of live mice, the team succeeded in visualizing targeted RNA in the cell nucleus. This fluorescent probe emits varying intensities of light depending on RNA concentration levels enabling the team to effectively quantitatively analyze RNA in the living body. The imaging technique, for the first time in the world, quantitatively conveyed that the RNA behavior in live tissue differed from that of a cultured cell when a drug was administered.

Wang hopes that this new imaging technique can help reveal "the natural state of RNA," that allows us to observe the emergence and disappearance of RNA clusters in many types of species, including those that cannot be genetically engineered. "Our next goal is to investigate differences of RNA activity in a live, single cell, what regulates RNA activity, and compare healthy tissue and unhealthy tissue to elucidate gene expression mechanisms and pathologies caused by abnormal RNA activity."